DLG3 discs large MAGUK scaffold protein 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DLG3provided by HGNC
Official Full Name: discs large MAGUK scaffold protein 3provided by HGNC
Primary source: HGNC:HGNC:2902
See related: Ensembl:ENSG00000082458 MIM:300189; AllianceGenome:HGNC:2902
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MRX; XLMR; MRX90; NEDLG; SAP102; XLID90; PPP1R82
Summary: This gene encodes a member of the membrane-associated guanylate kinase protein family. The encoded protein may play a role in clustering of NMDA receptors at excitatory synapses. It may also negatively regulate cell proliferation through interaction with the C-terminal region of the adenomatosis polyposis coli tumor suppressor protein. Mutations in this gene have been associated with X-linked cognitive disability. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]
Expression: Ubiquitous expression in brain (RPKM 7.8), colon (RPKM 6.2) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xq13.1

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (70444835..70505490)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (68878160..68938810)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (69664685..69725340)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Identification of a DLG3 stop mutation in the MRX20 family.
Title: Identification of a DLG3 stop mutation in the MRX20 family.
Silence of lncRNA MIAT-mediated inhibition of DLG3 promoter methylation suppresses breast cancer progression via the Hippo signaling pathway.
Title: Silence of lncRNA MIAT-mediated inhibition of DLG3 promoter methylation suppresses breast cancer progression via the Hippo signaling pathway.
High expression of DLG3 is associated with decreased survival from breast cancer.
Title: High expression of DLG3 is associated with decreased survival from breast cancer.
These data provide evidence for a novel mechanism in regulating SAP102 function and glutamate receptor trafficking.
Title: Regulation of SAP102 Synaptic Targeting by Phosphorylation.
This family broadens the mutational and phenotypical spectrum of DLG3-associated non-syndromic X-linked intellectual disability and demonstrates that heterozygous female mutation carriers can be as severely affected as males.
Title: Skewed X-inactivation in a family with DLG3-associated X-linked intellectual disability.
Following the critical period NMDA receptor function was unaffected by loss of SAP102 but there was a reduction in the divergence of TC connectivity. These data suggest that changes in synaptic function early in development caused by mutations in SAP102 result in changes in network connectivity later in life.
Title: Altered thalamocortical development in the SAP102 knockout model of intellectual disability.
The dupG DLG3 variant segregated with non-syndromic X-linked intellectual disability in a large family and was predicted to disrupt folding of the mRNA.
Title: A non-coding variant in the 5' UTR of DLG3 attenuates protein translation to cause non-syndromic intellectual disability.
Insertion of a guanine into the DLG3 5' UTR, 7 bp upstream of the start codon, down regulated DLG3 protein levels. This non-coding variant segregates with X-linked intellectual disability in a large family.
Title: A non-coding variant in the 5' UTR of DLG3 attenuates protein translation to cause non-syndromic intellectual disability.
Trans-homophilic interaction of CADM1 activates PI3K by forming a complex with MAGuK-family proteins MPP3 and Dlg.
Title: Trans-homophilic interaction of CADM1 activates PI3K by forming a complex with MAGuK-family proteins MPP3 and Dlg.
miR-1246 might play a role in neurological pathogenesis of human enterovirus 71 by regulating DLG3 gene in infected cells.
Title: Parallel mRNA and microRNA profiling of HEV71-infected human neuroblastoma cells reveal the up-regulation of miR-1246 in association with DLG3 repression.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Intellectual disability, X-linked 90 MedGen: C3275443 OMIM: 300850 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2024-04-25) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2024-04-25) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

DXS7496 (e-PCR)
- UniSTS:32561

RH36026 (e-PCR)
- UniSTS:30589

DXS348 (e-PCR)
- UniSTS:150186

SGC33537 (e-PCR)
- UniSTS:74420

SGC30680 (e-PCR)
- UniSTS:21447

DLG3_4190 (e-PCR)
- UniSTS:466133

DXS8107 (e-PCR), detects polymorphism
- UniSTS:46317

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ionotropic glutamate receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables kinase binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatase binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in establishment of planar polarity	IEA Inferred from Electronic Annotation more info
involved_in establishment or maintenance of epithelial cell apical/basal polarity	IBA Inferred from Biological aspect of Ancestor more info
involved_in establishment or maintenance of epithelial cell apical/basal polarity	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of cell population proliferation	NAS Non-traceable Author Statement more info	PubMed
involved_in nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to synapse	IBA Inferred from Biological aspect of Ancestor more info
involved_in receptor clustering	IBA Inferred from Biological aspect of Ancestor more info
involved_in receptor localization to synapse	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of postsynaptic membrane neurotransmitter receptor levels	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of AMPA glutamate receptor complex	IEA Inferred from Electronic Annotation more info
located_in adherens junction	NAS Non-traceable Author Statement more info	PubMed
is_active_in basolateral plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in bicellular tight junction	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in neuromuscular junction	IBA Inferred from Biological aspect of Ancestor more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
is_active_in postsynaptic density membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: disks large homolog 3

Names: discs, large homolog 3; neuroendocrine-DLG; protein phosphatase 1, regulatory subunit 82; synapse-associated protein 102

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_015849.2 RefSeqGene

Range

4981..65636

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166278.2 → NP_001159750.1 disks large homolog 3 isoform c

See identical proteins and their annotated locations for NP_001159750.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. Translation initiates at a downstream AUG and results in an isoform (c) that is shorter than isoform a.

Source sequence(s)

AB033058, AK303377, CK300381

Consensus CDS

CCDS55439.1

UniProtKB/Swiss-Prot

Q92796

Related

ENSP00000441393.1, ENST00000542398.1

Conserved Domains (2) summary

pfam00625
Location:175 → 353

Guanylate_kin; Guanylate kinase

cl17036
Location:19 → 85

SH3; Src Homology 3 domain superfamily
NM_020730.3 → NP_065781.1 disks large homolog 3 isoform b

See identical proteins and their annotated locations for NP_065781.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. Translation initiates at an alternate AUG and results in an isoform (b) that is shorter and has a distinct N-terminus compared to isoform a.

Source sequence(s)

AB033058, AL139398, CK300381, CN357435

Consensus CDS

CCDS43967.1

UniProtKB/Swiss-Prot

Q92796

Related

ENSP00000363475.3, ENST00000374355.8

Conserved Domains (3) summary

cd00992
Location:47 → 125

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam00625
Location:321 → 499

Guanylate_kin; Guanylate kinase

cl17036
Location:165 → 231

SH3; Src Homology 3 domain superfamily
NM_021120.4 → NP_066943.2 disks large homolog 3 isoform a

See identical proteins and their annotated locations for NP_066943.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).

Source sequence(s)

AB033058, AB209328, AL139398, BC093866, CK300381

Consensus CDS

CCDS14403.1

UniProtKB/Swiss-Prot

B4E0H1, D3DVU5, Q5JUW6, Q5JUW7, Q92796, Q9ULI8

UniProtKB/TrEMBL

Q5JUW8

Related

ENSP00000363480.3, ENST00000374360.8

Conserved Domains (5) summary

cd12029
Location:502 → 568

SH3_DLG3; Src Homology 3 domain of Disks Large homolog 3

cd00992
Location:384 → 462

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam00625
Location:626 → 804

Guanylate_kin; Guanylate kinase

pfam10600
Location:311 → 385

PDZ_assoc; PDZ-associated domain of NMDA receptors

pfam10608
Location:52 → 130

MAGUK_N_PEST; Polyubiquitination (PEST) N-terminal domain of MAGUK

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

70444835..70505490

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006724625.3 → XP_006724688.1 disks large homolog 3 isoform X1

See identical proteins and their annotated locations for XP_006724688.1

UniProtKB/TrEMBL

Q5JUW8

Conserved Domains (5) summary

cd12029
Location:502 → 568

SH3_DLG3; Src Homology 3 domain of Disks Large homolog 3

cd00992
Location:384 → 462

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam00625
Location:658 → 836

Guanylate_kin; Guanylate kinase

pfam10600
Location:311 → 385

PDZ_assoc; PDZ-associated domain of NMDA receptors

pfam10608
Location:52 → 130

MAGUK_N_PEST; Polyubiquitination (PEST) N-terminal domain of MAGUK
XM_011530883.2 → XP_011529185.1 disks large homolog 3 isoform X2

UniProtKB/TrEMBL

Q5JUW8

Conserved Domains (5) summary

cd12029
Location:502 → 568

SH3_DLG3; Src Homology 3 domain of Disks Large homolog 3

cd00992
Location:384 → 462

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam00625
Location:644 → 822

Guanylate_kin; Guanylate kinase

pfam10600
Location:311 → 385

PDZ_assoc; PDZ-associated domain of NMDA receptors

pfam10608
Location:52 → 130

MAGUK_N_PEST; Polyubiquitination (PEST) N-terminal domain of MAGUK
XM_006724626.3 → XP_006724689.1 disks large homolog 3 isoform X3

See identical proteins and their annotated locations for XP_006724689.1

UniProtKB/TrEMBL

Q5JUW8

Related

ENSP00000194900.4, ENST00000194900.8

Conserved Domains (5) summary

cd12029
Location:502 → 568

SH3_DLG3; Src Homology 3 domain of Disks Large homolog 3

cd00992
Location:384 → 462

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam00625
Location:640 → 818

Guanylate_kin; Guanylate kinase

pfam10600
Location:311 → 385

PDZ_assoc; PDZ-associated domain of NMDA receptors

pfam10608
Location:52 → 130

MAGUK_N_PEST; Polyubiquitination (PEST) N-terminal domain of MAGUK
XM_017029322.3 → XP_016884811.1 disks large homolog 3 isoform X4
XM_017029323.3 → XP_016884812.1 disks large homolog 3 isoform X5
XM_017029324.3 → XP_016884813.1 disks large homolog 3 isoform X6
XM_005262248.5 → XP_005262305.1 disks large homolog 3 isoform X8

See identical proteins and their annotated locations for XP_005262305.1

UniProtKB/Swiss-Prot

Q92796

Conserved Domains (2) summary

pfam00625
Location:175 → 353

Guanylate_kin; Guanylate kinase

cl17036
Location:19 → 85

SH3; Src Homology 3 domain superfamily
XM_047441886.1 → XP_047297842.1 disks large homolog 3 isoform X8
XM_047441885.1 → XP_047297841.1 disks large homolog 3 isoform X8
XM_047441884.1 → XP_047297840.1 disks large homolog 3 isoform X8
XM_047441887.1 → XP_047297843.1 disks large homolog 3 isoform X8
XM_047441888.1 → XP_047297844.1 disks large homolog 3 isoform X9
XM_017029327.2 → XP_016884816.1 disks large homolog 3 isoform X10
XM_047441883.1 → XP_047297839.1 disks large homolog 3 isoform X8
XM_017029325.3 → XP_016884814.1 disks large homolog 3 isoform X7